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Microorganisms · 2020 ·Vol. 8 ·期 2 ·211 · IF 4.152

The Dysbiosis of Gut Microbiota Caused by Low-Dose Cadmium Aggravate the Injury of Mice Liver through Increasing Intestinal Permeability

Yehao Liu,Yuhui Li,Yuhong Xia,Kaiyong Liu,Lingling Ren,Yanli Ji

Cadmium (Cd), widely present in food and drinking water at low doses, can cause health risks. However, the mechanistic effects of long-term Cd exposure at low dose through dietary intake is poorly studied. The aim of this study is to elucidate whether the dysbiosis of gut microbiota caused by Cd at an environmental low dose can aggravate the injury of mice liver, and the possible mechanism is investigated. In order to explore the potential underlying mechanism, the analyses of the variation of gut microbiota composition, intestinal permeability, and hepatic transcriptome were conducted. Our results showed that gut microbiota was disturbed. The rise of intestinal permeability induced by the dysbiosis of gut microbiota resulted in more Cd ions accumulating in mice liver, but it could be restored partly through depleting gut microbiota by antibiotics cocktail. Transcriptomic analyses indicated that 162 genes were significantly differentially expressed including 59 up-regulated and 103 down-regulated in Cd treatment. These genes were involved in several important pathways. Our findings provide a better understanding about the health risks of cadmium in the environment.Keywords:transcriptome analyses;gut microbiota;cadmium;intestinal permeability

CAS / MDL: 10108-64-2
研究领域: 环境健康 · 微生物学 · 分子生物学 · 毒理学
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Gut Microbes · 2025 · IF 11

Uncovering de novo polyamine biosynthesis in the gut microbiome and its alteration in inflammatory bowel disease

Xinwei Li,Xia Xiao,Shengnan Wang,Biyu Wu,Yixuan Zhou,Pan Deng

Polyamines are important gut microbial metabolites known to affect host physiology, yet the mechanisms behind their microbial production remain incompletely understood. In this study, we developed a stable isotope-resolved metabolomic (SIRM) approach to track polyamine biosynthesis in the gut microbiome. Viable microbial cells were extracted from fresh human and mouse feces and incubated anaerobically with [U-13C]-labeled inulin (tracer). Liquid chromatography-high resolution mass spectrometry analysis revealed distinct 13C enrichment profiles for spermidine (SPD) and putrescine (PUT), indicating that the arginine-agmatine-SPD pathway contributes to SPD biosynthesis in addition to the well-known spermidine synthase pathway (PUT aminopropylation). Species differences were observed in the 13C enrichments of polyamines and related metabolites between the human and mouse microbiome. By analyzing the fecal metabolomics and metatranscriptomic data from an inflammatory bowel disease (IBD) cohort, we found significantly higher polyamine levels in IBD patients compared to healthy controls. Further investigations using single-strain SIRM and in silico analyses identified Bacteroides spp. as key contributors to polyamine biosynthesis, harboring essential genes for this process and potentially driving the upregulation of polyamines in IBD. Taken together, this study expands our understanding of polyamine biosynthesis in the gut microbiome and will facilitate the development of precision therapies to target polyamine-associated diseases.

CAS / MDL: 64-77-7
研究领域: 微生物学 · 代谢组学 · 医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Nutrients · 2023 ·Vol. 15 ·期 19 ·4176 · IF 5.9

Red Rice Seed Coat Targeting SPHK2 Ameliorated Alcoholic Liver Disease via Restored Intestinal Barrier and Improved Gut Microbiota in Mice

Yuxu Chen,Zhiye Zhao,Shancheng Guo,Yaxian Li,Haiaolong Yin,Lei Tian,Guiguang Cheng,Ye Li

Alcoholic liver disease (ALD), leading to the most common chronic liver diseases, is increasingly emerging as a global health problem, which is intensifying the need to develop novel treatments. Herein, our work aimed to estimate the therapeutic efficacy of red rice (Oryza sativaL.) seed coat on ALD and further uncover the underlying mechanisms. Red rice seed coat extract (RRA) was obtained with citric acid–ethanol and analyzed via a widely targeted components approach. The potential targets of RRA to ALD were predicted by bioinformatics analysis. Drunken behavior, histopathological examination, liver function, gut microbiota composition and intestinal barrier integrity were used to assess the effects of RRA (RRAH, 600 mg/kg·body weight; RRAL, 200 mg/kg·body weight) on ALD. Oxidative stress, inflammation, apoptosis associated factors and signaling pathways were measured by corresponding kits, Western blot and immunofluorescence staining. In ALD model mice, RRA treatment increased sphingosine kinase 2 (SPHK2) and sphingosine-1-phosphate (S1P) levels, improved gut microbiota composition, restored intestinal barrier, decreased lipopolysaccharide (LPS) levels in plasma and the liver, cut down Toll-like receptor 4 (TLR4)/Nuclear factor kappa B (NF-κB) pathways, alleviated liver pathological injury and oxidative stress, attenuated inflammation and apoptosis and enhanced liver function. To sum up, RRA targeting SPHK2 can ameliorate ALD by repairing intestinal barrier damage and reducing liver LPS level via the TLR4/NF-κB pathway and intestinal microbiota, revealing that red rice seed coat holds potential as a functional food for the prevention and treatment of ALD.Keywords:red rice seed coat;alcoholic liver disease;SPHK2;gut microbiota;intestinal barrier

CAS / MDL: 65666-07-1
研究领域: 药理学 · 胃肠病学 · 微生物学 · 营养学
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MOLECULAR NUTRITION & FOOD RESEARCH · 2025 · IF 4.2

Effects of 1,3-Dioleoyl-2-palmitoylglycerol on Intestine Structural and Functional Development in Early Life

Fang Wu,Yaqiong Liu,Ming Zhang,Xinlei Yuan,Yutong Jin,Yixuan Li,Ran Wang,Yanling Hao,Bing Fang

1,3-Dioleoyl-2-palmitoyl-glycerol (OPO) is a specific triglyceride in human breast milk, and it has been added to infant formula to mimic human breast milk fat. Existing studies only focused on its effects on fatty acid and calcium absorption, as well as the intestinal microbial composition; however, effects of OPO on the early-life development of intestine were still unclear. Our study explored the effects of OPO on intestinal epithelial structure and barrier construction in neonatal mice and the involvement of intestinal microorganisms. OPO supplementation significantly increased the number of intestinal stem cells, which in turn promoted villus and crypt, and promoted goblet cell and Paneth cell differentiation. OPO also promotes epithelial barrier integrity by increasing the expression of mucin 2, lysozyme 1, and tight junction proteins. Furthermore, the benefits of OPO were associated with the higher abundance of beneficial bacteria ( unclassified_f_Muribaculaceae , Akkermansia , Bifidobacterium , and Blautia ) and elevated butyrate levels. This study demonstrates the efficacy of OPO on intestinal health in neonatal mice beyond defecation, expands the understanding of the biological functions of OPO, and expands its application in intestinal health products targeting special populations, such as the elderly or individuals with intestinal fragility or injury.

研究领域: 营养学 · 肠道健康 · 微生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Food Bioscience · 2025 · IF 5.9

Sulfated mulberry (Morus atropurpurea Roxb.) leaf polysaccharide ameliorates dextran sodium sulfate-induced colitis via regulation of gut microbiota and intestinal barrier integrity

Wendong Liu,Weidong Zhang,Mingyue Shen,Zhikang Xiong,Jianhua Xie

Ulcerative colitis (UC), a chronic inflammatory bowel disease with increasing global incidence, necessitates novel dietary interventions from sustainable sources. This study investigated a dietary polysaccharide (MLP) extracted from mulberry ( Morus atropurpurea Roxb.) leaf and its sulfated derivative (SMLP) synthesized via the sulfur trioxide-pyridine method. SMLP significantly ameliorated dextran sodium sulfate (DSS)-induced colitis in mice, attenuating weight loss, disease activity index, colon shortening, and histopathological damage compared to MLP. Mechanistically, SMLP enhanced intestinal barrier integrity (upregulated ZO-1 and MUC2 expression), increased the IL-10, decreased TNF-α and IL-1β expression, and targeted modulation of the gut microbiota-metabolite axis. SMLP specifically enriched Akkermansia muciniphila (Verrucomicrobiota) and augmented immunoregulatory short-chain fatty acids (SCFAs: acetate, propionate). Crucially, sulfation modification significantly potentiated the efficacy of MLP. This work establishes a mechanistic basis for utilizing edible plant polysaccharides, particularly through structure-guided chemical modification like sulfation, as high-value functional food ingredients against inflammation-related gastrointestinal disorders.

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Carbohydrate Polymer Technologies and Applications · 2025 · IF 6.5

Possibility of alleviating dextran sulfate sodium-induced colitis in mice by modulate intestinal barrier function and gut microbiota with laminarin acetyl esters

Kit-Leong Cheong,Amanullah Sabir,Suresh Veeraperumal,Franck Quero,Rui Li,Qiaoli Zhao,Karsoon Tan,Saiyi Zhong,Udayakumar Veerabagu

This study investigates the esterification of laminarin, a β-glucan polysaccharide, using trifluoroacetic anhydride and acetic acid to synthesize laminarin acetyl esters (LA) with potential therapeutic properties. The efficacy of LA was evaluated in an in vivo dextran sulfate sodium induced colitis mouse model. Treatment with LA significantly improved the organ index and modulated inflammatory responses by upregulating anti-inflammatory cytokines, such as IL-10 and TGF-β1. LA also promoted a favorable shift in gut microbiota composition, notably increasing the relative abundance of beneficial bacteria like Lactobacillus and Bifidobacterium , and enhancing short-chain fatty acid production, particularly acetic acid. Immunohistochemical analysis revealed a reduction in CD68 expression and an elevation in CD163 expression, indicating a shift toward an anti-inflammatory macrophage phenotype. These findings demonstrate that LA mitigates pro-inflammatory responses, enhances gut barrier integrity, and supports a healthy gut microbiota, underscoring its potential as a therapeutic agent for managing colitis and improving gut health.

研究领域: 医学 · 免疫学 · 微生物学
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Food & Function · 2020 ·Vol. 11 ·期 9 ·8259-8272 · IF 4.171

Identification of polyphenol from Ziziphi spinosae semen against human colon cancer cells and colitis-associated colorectal cancer in mice

Shuhua Shan,Yue Xie,Chengying Zhang,Bin Jia,Hanqing Li,Zhuoyu Li

Homology of medicine and food-zizyphi spinosi semen (ZSS) exhibits abundant pharmacological activities, such as sedation, hypnosis and anti-depression. In the present study, the water soluble polyphenols extracted from ZSS via the acid digestion method were named ZSSP, and exhibited significant anti-colorectal cancer (CRC) activity, characterized by restraining cell proliferation, promoting cell apoptosis and increasing chemo-sensitivity of CRC cells. The potential of ZSSP in vivo was further evaluated in an AOM/DSS-induced colitis-associated carcinogenesis (CAC) mouse model. Intriguingly, ZSSP diminished the number and volume of CAC polyps in mice in a dose-dependent manner, and effectively limited the damage of mice organs induced by AOM/DSS. The immunohistochemistry result showed that the elevated CRC early markers in CAC mice, such as COX-II, EMR1, and Ki67, were potently prevented by the ZSSP treatment. Further, the component in ZSSP with the anti-CRC activity was identified as spinosin by the macroporous resin of SP207 and RP-HPLC-MS/MS. Interestingly, during the extraction process, sodium ions were introduced forming spinosin·Na+, which had better water solubility and more remarkable anti-CRC activity than the spinosin. This study provides a new pharmacological property of spinosin derived from ZSS, inhibiting the growth of human CRC cells and colitis-associated CRC in mice, which indicates its potential use as a natural agent against CRC.

CAS / MDL: 51-21-8
研究领域: 肿瘤学 · 药理学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF ETHNOPHARMACOLOGY · 2023 · IF 5.4

Echinacoside inhibits colorectal cancer metastasis via modulating the gut microbiota and suppressing the PI3K/AKT signaling pathway

Jiao Wei,Zongmei Zheng,Xinxin Hou,Fengjing Jia,Yuan Yuan,Fuwen Yuan,Feng He,Liang Hu,Ling Zhao

Ethnopharmacological relevance Echinacoside (ECH) is the dominant phenylethanoid glycoside-structured compound identified from our developed herbal formula Huangci granule, which has been previously reported to inhibit the invasion and metastasis of CRC and prolong patients’ disease-free survival duration. Though ECH has inhibitory activity against aggressive colorectal cancer (CRC) cells, its anti-metastasis effect in vivo and the action mechanism is undetermined. Given that ECH has an extremely low bioavailability and gut microbiota drives the CRC progression, we hypothesized that ECH could inhibit metastatic CRC by targeting the gut microbiome . Aim of the study The purpose of this study was to investigate the impact of ECH on colorectal cancer liver metastasis in vivo and its potential mechanisms. Materials and methods An intrasplenic injection-induced liver metastatic model was established to examine the efficiency of ECH on tumor metastasis in vivo . Fecal microbiota from the model group and the ECH group were separately transplanted into pseudo-sterile CRLM mice in order to verify the role of gut flora in the ECH anti-metastatic effect. The 16S rRNA gene sequence was applied to analyze the structure and composition of the gut microbiota after ECH intervention, and the effect of ECH on short-chain fatty acid (SCFAs)-producing bacteria growth was proven by anaerobic culturing in vitro . GC-MS was applied to quantitatively analyze the serum SCFAs levels in mice. RNA-seq was performed to detect the gene changes involving tumor-promoting signaling pathway. Results ECH inhibited CRC metastasis in a dose-dependent manner in the metastatic colorectal cancer (mCRC) mouse model. Manipulation of gut bacteria in the mCRC mouse model further proved that SCFA-generating gut bacteria played an indispensable role in mediating the antimetastatic action of ECH. Under an anaerobic condition, ECH benefited SCFA-producing microbiota without affecting the total bacterial load, presenting a dose-dependent promotion on the growth of a butyrate producer, Faecalibacterium prausnitzii ( F.p ). Furthermore, ECH-reshaped or F.p -colonized microbiota with a high butyrate-producing capability inhibited liver metastasis by suppressing PI3K/AKT signaling and reversing the epithelial-mesenchymal transition (EMT) process, whereas this anti-metastatic ability was abrogated by the butyrate synthase inhibitor heptanoyl-CoA. Conclusion This study demonstrated that ECH exhibits oral anti-metastatic efficacy by facilitating butyrate-producing gut bacteria, which downregulates PI3K/AKT signaling and EMT. It hints at a novel role for ECH in CRC therapy.

研究领域: 药理学 · 肿瘤学 · 微生物学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Journal of Animal Science and Biotechnology · 2023 ·Vol. 14 ·期 1 ·1-17 · IF 7

Enterogenic Stenotrophomonas maltophilia migrates to the mammary gland to induce mastitis by activating the calcium-ROS-AMPK-mTOR-autophagy pathway

He Zhaoqi,Zhao Caijun,He Yuhong,Liu Zhuoyu,Fan Guyue,Zhu Kun,Wang Yiqi,Zhang Naisheng,Fu Yunhe,Hu Xiaoyu

Background Mastitis is an inflammatory disease of the mammary gland that has serious economic impacts on the dairy industry and endangers food safety. Our previous study found that the body has a gut/rumen-mammary gland axis and that disturbance of the gut/rumen microbiota could result in ‘gastroenterogenic mastitis’. However, the mechanism has not been fully clarified. Recently, we found that long-term feeding of a high-concentrate diet induced mastitis in dairy cows, and the abundance of Stenotrophomonas maltophilia (S. maltophilia) was significantly increased in both the rumen and milk microbiota. Accordingly, we hypothesized that ‘gastroenterogenic mastitis’ can be induced by the migration of endogenous gut bacteria to the mammary gland. Therefore, this study investigated the mechanism by which enterogenic S. maltophilia induces mastitis.Results First, S. maltophilia was labelled with superfolder GFP and administered to mice via gavage. The results showed that treatment with S. maltophilia promoted the occurrence of mastitis and increased the permeability of the blood-milk barrier, leading to intestinal inflammation and intestinal leakage. Furthermore, tracking of ingested S. maltophilia revealed that S. maltophilia could migrate from the gut to the mammary gland and induce mastitis. Subsequently, mammary gland transcriptome analysis showed that the calcium and AMPK signalling pathways were significantly upregulated in mice treated with S. maltophilia. Then, using mouse mammary epithelial cells (MMECs), we verified that S. maltophilia induces mastitis through activation of the calcium-ROS-AMPK-mTOR-autophagy pathway.Conclusion sIn conclusion, the results showed that enterogenic S. maltophilia could migrate from the gut to the mammary gland via the gut-mammary axis and activate the calcium-ROS-AMPK-mTOR-autophagy pathway to induce mastitis. Targeting the gut-mammary gland axis may also be an effective method to treat mastitis.

CAS / MDL: 9005-64-5
研究领域: 兽医学 · 微生物学 · 免疫学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MOLECULAR NUTRITION & FOOD RESEARCH · 2023 · IF 5.2

Remodeling of Gut Microbiota by Probiotics Alleviated Heat Stroke-Induced Necroptosis in Male Germ Cells

Hui Cai,Dezhe Qin,Yundie Liu,Xinrui Guo,Yang Liu,Baohua Ma,Jinlian Hua,Sha Peng

Scope Systemic heat stress (or heatstroke; HS) induces germ cell death and spermatogenesis disorders in men and male mammals. Also, it affects the immune environment of the circulatory system promoting gut inflammation and intestinal permeability, leading to pathogenic infection. In this study, the crosstalk between the gut and testis (gut-testis axis) under HS is explored, by examining the effects of intestinal immune status on the health of the male reproductive system in mice. Methods and results A mouse model of systemic heat stress is established to investigate the effect of probiotics on testis health. The results reveal that pro-inflammatory factor receptor activation pathway and pathogen infection response pathway are significantly upregulated in HS testes, leading to necroptosis, while pro-inflammatory factor and endotoxin are detected locally in the intestine and then entered the blood. The study then uses probiotics to intervene in gut microbiota, which results in milder gut microbial changes, lower inflammatory responses in the HS gut, and less necroptosis in the HS testes. Conclusion Probiotics-based remodeling of gut microbiota (GM) reduces the proliferation of abnormal bacteria and decreases the spread of gut-derived inflammatory mediators into the blood circulation under long-term systemic heat stress, which relieves inflammation on germ cells.

CAS / MDL: 518-47-8
研究领域: 生殖生物学 · 免疫学 · 微生物学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Food Bioscience · 2024 · IF 4.8

Amelioration effects of chlorogenic acid on mice colitis: Anti-inflammatory and regulation of gut flora

Peng Xu,Shuai Chen,Qi Fu,Siyi Zhu,Zheng Wang,Jie Li

This research endeavors to investigate the potential preventive and protective effects of chlorogenic acid (CGA), a bioactive component found in various foods, in the context of dextran sodium sulfate (DSS)-induced colitis in mice. The study reveals that CGA administration, at dosages of 150 and 300 mg/kg, significantly retards the progression of colitis. This is substantiated by observable enhancements in colon length, reduction in the disease activity index, and mitigation of colon tissue damage. Meanwhile, CGA acts as an antioxidant by reducing the oxidative stress associated with colitis inflammation and increasing the activity of antioxidant enzymes. Furthermore, CGA demonstrates anti-inflammatory properties by inhibiting the inflammatory response associated with colitis and regulating the excessive expression of cytokines. Notably, CGA contributes to the restoration of intestinal barrier function by augmenting the levels of claudin-1 and ZO-1. Moreover, the investigation uncovers CGA's capacity to modulate the gut microbiota composition in colitic mice, fostering the proliferation of beneficial bacteria, notably Lactobacillus , while concurrently impeding the growth of detrimental bacteria like Bacteroides , Enterobacteriaceae, and Escherichia_Shigella . To conclude, these findings substantiate the viability of CGA for diverse applications in the realms of food and medicine, thereby bolstering its potential as a therapeutic strategy within dietary interventions.

CAS / MDL: 327-97-9
研究领域: 药理学 · 免疫学 · 胃肠病学 · 微生物学
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EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES · 2020 · IF 3.616

Modulation of gut microbiota and intestinal metabolites by lactulose improves loperamide-induced constipation in mice

Xiaoyu Zhang,Junping Zheng,Nan Jiang,Guangjun Sun,Xinkun Bao,Mingwang Kong,Xue Cheng,Aizhen Lin,Hongtao Liu

Lactulose is a common laxative and has been widely applied to clinical treatment for constipation. This study aimed to explore the improving effect of lactulose on constipation through the mediation of gut microbiota and intestinal metabolites. BALB/c mice with constipation induced by loperamide were orally treated with lactulose for four weeks. After the treatment, the constipation-related factors were determined. The effect of lactulose on the composition of gut microbiota was assessed by 16S rDNA gene sequencing. Gas chromatography or liquid chromatography-mass spectrometer (GC/LC-MS) analysis was used for the quantification of intestinal metabolites. The treatment of constipated mice with lactulose accelerated intestinal motility, suppressed inflammatory responses, protected gut barrier, and improved metabolisms of water and salt in the intestinal tract. These therapeutic effects were attributed to the reversed gut microbiota dysfunction, which conferred the benefit to the production of intestinal metabolites including bile acids, short-chain fatty acids, and tryptophan catabolites. Further, the depletion of intestinal flora from loperamide- or (loperamide + lactulose)-treated mice confirmed the significance of gut microbiota in the mediation of constipation. In summary, this study leads us to propose that lactulose may improve constipation through a prebiotic effect on gut microbiota and intestinal metabolites.

研究领域: 胃肠病学 · 微生物学 · 药理学 · 代谢组学
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